Phase II Study of Sunitinib in Tumors With c-KIT Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V.

Purpose: The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring c-KIT mutations.

Methods: EAY131-V, is an open-label, single-arm, phase II study. Eligible patients had malignancies containing somatic c-KIT mutation on exons 9, 11, 13, or 14. Exclusions were mutations on exons 17 and 18, gastrointestinal stromal tumors, renal cell carcinoma, and pancreatic neuroendocrine tumors. Patients received sunitinib 50 mg orally once daily for 4 weeks with 2-week rest per cycle, until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR); secondary end points were progression-free survival (PFS) at 6 months, PFS, overall survival, and toxicities.

Results: Between November 1, 2016, and May 21, 2020, 10 patients were enrolled and nine were eligible and started treatment. The median age was 62 years (range, 30-76), 77.8% received two previous lines of systemic therapy, and 22.2% received >3 lines. The most common histology was melanoma (44%) and then squamous cell carcinoma of the lung or thymus (33%). There were two partial responses with an ORR of 22.2% (90% CI, 4.1 to 55) and stable disease in 44%. All patients demonstrated tumor shrinkage of target lesions. The estimated 6-month PFS was 33.3% (90% CI, 15.4 to 72.4). Grade 3-4 toxicities occurred in five patients (55.6%). This arm was closed in 2022 on the basis of low accrual. Prevalence of eligible c-KIT mutations after screening 5,540 patients was 0.45%.

Conclusion: Sunitinib for c-KIT mutations did not meet the primary end point, but in this small sample size, a potential signal cannot be ruled out. Rate of eligible c-KIT mutations was low, affecting accrual to this arm.